Regression Of Bone Metastases Research Articles

High-grade Endometrial Carcinomas With Solid Basaloid Morphology and Geographic Necrosis Lacking Definitive Pilomatrix-like Features: Clinicopathologic Characteristics Including Aggressive Behavior and Novel Molecular Events.

High-grade endometrioid carcinomas occasionally demonstrate solid basaloid morphology with geographic necrosis (SB-GN). This pattern is among the defining features of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC), a recently proposed tumor type which is additionally characterized by the presence of shadow cells, abnormal beta-catenin/CTNNB1 mutations, strong CDX2 expression, and poor outcomes. Clinicopathologic overlap between PiMHEC and other high-grade endometrial cancers with SB-GN has not been established. We screened 300 endometrial carcinomas on tissue microarray for SB-GN histology and performed a detailed whole-section morphologic review, immunohistochemical analysis, and next-generation sequencing on all cases bearing this pattern. Four (1.3%) demonstrated SB-GN. All 3 with clinical follow-up had extremely aggressive behavior despite being MMR-deficient; in contrast, only 27% of other MMR-deficient high-grade carcinomas recurred. One SB-GN case met most of the previously outlined diagnostic criteria for PiMHEC including abnormal beta-catenin/CTNNB1 (p.S37P variant) and strong CDX2 expression; notably, however, shadow cells were absent. This case also demonstrated a KRAS p.A59T pathogenic variant. The other 3 cases also lacked shadow cells; the 2 with sequencing data bore no CTNNB1 abnormalities but showed likely oncogenic variants involving the pilomatrixoma-associated gene FGFR2. All 3 cases with molecular results also bore somatic Notch pathway (NOTCH1/NOTCH2/NOTCH3) variants. The single case treated with immunotherapy showed complete and sustained response with regression of bone metastases despite abnormal beta-catenin/CTNNB1, which has been associated with immunotherapeutic resistance. These data suggest that the SB-GN pattern may connote a poor prognosis even in the absence of overt pilomatrix-like differentiation, and that novel molecular events may have implications for the treatment of these tumors.

Metronomic chemotherapy for hormone refractory prostate cancer (HRPC)

15649 Background: Low dose continuous chemotherapy (metronomic chemotherapy) is trying to many advanced cancers. Metronomic chemotherapy has important anti-angiogenic activity to tumor vessels. For patients who progressed after docetaxel, no standard options exist. We have experienced complete regression of bone metastases on super scan by low does cisplatin, UFT, diethylstilbestrol, and dexamethasone (CUDD) in a patient with HRPC (Int JCO, 8,118, 2003). Methods: CUDD consisting of weekly 5 mg/body of cisplatin plus 125 mg/body of diethylstilbestrol and daily 300–450 mg of UFT/day plus 0.5–1 mg of dexamethasone were given to 47 HRPC patients, (median and range of age: 66 and 52–72, respectively). The ECOG performance status was 0 to 1. Gleason score was 7 in 10 patients and 8 in 17 patients and 9 in 20 patients, respectively. Metastatic site was bone in 45 (EOD grade 1:10, 2:18, 3: 15, 4:2), lymph node in 8. Six cases became refractory to docetaxel were treated with CUDD plus CPM (50 mg/day). Results: Among the 45 patients assessable for bone metastasis, 12 (27 %) obtained marked improvement on bone scan. One was EOD grade 4 (super bone scan) and 9 were EOD grade 1–3. Eighteen (40 %) were stable and 15 (33%) progressed on bone scan. Among 8 patients of lymph node metastasis, 3 (38%) showed partial response, 2 (25%) no change and 3 (38%) progression. Twenty-five (53 %) out of 47 patients showed a PSA decline of 50% or greater. Among the 25 patients assessable for bone pain, 7 (28%) improved, 12 (48%) remained stable and 6 (24%) progressed. Their median response duration and median survival time were 8 months (range; 2 to 44 months) and 20 months (range, 4 to 48 months), respectively. Their median response duration was 3 months. Three of 6 refractory to docetaxel were responded to CUDD plus CPM. Their median response duration was 10 months. Conclusions: CUDD is effective in almost half of hormone refractory prostate cancer patients and has advantage of minimal side effect. Three of 6 docetaxel refractory cases also responded to CUDD plus CPM. No significant financial relationships to disclose.

Regression of bone metastases following adoptive transfer of anti-CD3-activated and IL-2-expanded tumor vaccine draining lymph node cells

As many as 80% of patients with breast, prostate, or lung cancer develop bone metastases during the course of their illness. However, thus far, no attempts have been made to explore the potential value of adoptive immunotherapy with antigen-specific T lymphocytes specifically for the treatment of skeletal metastases. Here, we demonstrate tumor regression in a preclinical model of bone metastases from the murine B16BL6 melanoma following adoptive transfer of effector T lymphocytes obtained from tumor vaccine draining lymph nodes. The antitumor effect required transfer of high number of effector cells, which was dependent on CD8+ cells as demonstrated by in vivo depletion of different T cell subsets, and was magnified if effector cells were administered to the arterial supply of the bone/bone marrow. Using flow cytometric analysis, CFSE-labelled Thy1.1+ donor T cells were isolated from the bone marrow of tumor-bearing mice at 24 h and 6 days following adoptive transfer. At the latter time point cell division of the transferred effector cells was detectable. Currently, no curative treatment is known for skeletal metastases in clinical practice. Considering the promising early findings in the present study, further studies exploring the therapeutic potential of adoptive immunotherapy for metastatic disease to the skeleton are warranted.

Radiological evidence for regression of bone metastases during 89Sr treatment

Radiological evidence for regression of bone metastases during 89Sr treatment

Regression of Bone Metastases from Renal Cell Carcinoma Achieved by Combined Therapy

A case of renal cell carcinoma with successive multiple bone metastases which survived over a 36-month period is presented. A clinical and radiological regression of bone lesions was obtained by means of combined therapy (hormone therapy, radiotherapy, and immunotherapy), after the original tumor had been removed.